Regarding inflammatory diseases, various medicaments capable of inhibiting acute stage inflammations have been developed in recent years, but medicaments which can effectively inhibit chronic stage inflammations are still scarce so that their development is a pressing problem. Also, an anti-inflammatory drug which can be used without distinctions between acute stage and chronic stage is useful in the clinical field.
Under such circumstances, attempts are being made on the research and development of medicaments having phosphodiesterase IV (PDE (IV)) inhibitory activity. This is based on the information that PDE (IV) is concerned in acute and chronic inflammatory diseases (see for example, J. Pharmacol. Exp. Ther., 266(1), 306-313 (1993), Br. J. Pharmacol. , 120(2), 289-297 (1997) and Am. J. Respir. Crit. Care Med., 149(5), 1153-1159 (1994)). In reality, however, drugs so far developed merely having such an activity are effective for acute inflammatory diseases but cannot exert sufficient effects on chronic inflammatory diseases. It is considered that certain members of cytokine produced by Th2 cells as one of the subgroups of CD4.sup.+ T cells are taking an important role in the onset of inflammatory diseases, and interleukin (IL)-4 among them is particularly concerned in chronic stage inflammatory diseases (see for example, Am. J. Physiol., 272 (2 Pt 1), L 253-261 (1997), Am. J. Respir. Cell Mol. Biol. , 10(5), 526-532 (1994) and ibid., 13(1), 54-59 (1995)).
In consequence, development of a drug having both PDE (IV) inhibitory activity and IL-4 production inhibitory activity will result in an anti-inflammatory drug which is effective on both acute and chronic inflammatory diseases. At present, PDA-641 has been reported as such a compound (cf. Allergy Clin. Immunol., 93, 286 (1994)), but this compound is not satisfactory because of its weak IL-4 production inhibitory activity.
Benzimidazole derivatives have been broadly studies as medicaments. JP-A-3-14579 describes a benzimidazole derivative having an imidazole group and a triazole group, but the compound is disclosed only as a therapeutic agent for heart diseases and a therapeutic agent for duodenal ulcer, so that the compound has not been known as an anti-inflammatory agent (the term "JP-A" as used herein means an "unexamined published Japanese patent application"). International Publication No. WO 94/12461 describes a benzimidazole derivative which has PDE (IV) inhibitory activity and is used in various inflammatory diseases, but the benzimidazole derivative is different from the compound of the present invention in terms of the presence or absence of triazole ring on the condensed phenyl ring, and its effects on both acute and chronic inflammatory diseases are not as expected.
The present invention contemplates providing a compound which has both IL-4 production inhibitory activity and PDE (IV) inhibitory activity and is useful in treating or preventing acute and chronic inflammatory diseases.